Central Dogma Theory

bzoomImage

Transcription

Transcribers = transcription

Messenger RNA

Messenger Boy = Messenger RNA

Translation

Translator = Translation

Ribosomes

Two Chrome Zombies with ribs showing = Ribosomes

tRNA

Train = tRNA

Central Dogma Theory and Mutations

The central dogma of life consists of two main steps; transcription and translation. The nucleotide sequence present in the genes is responsible for the proper transformation of information from DNA to the ribosomes for the synthesis of new proteins. The alterations in the nucleotide sequences can produce different types of mutations. Out of these many types of mutations, one is the frame-shift mutation. Frame-shift mutation occurs when one or more nucleotide is either deleted from or added to the coding part of the gene. It will result in the radically different sequence of amino acids, or truncated product by the formation of termination codons by frame-shift mutation. Frame-shift mutations occur in diseases like Cystic fibrosis (CF), Tay-Sachs disease, Cancers, Crohn’s disease, and many others. The frame-shift mutations can be detected by fluorescence and sequencing. The cure for diseases produced by frame-shift mutation is under consideration of research work. shutterstock_106781666 shutterstock_532794004

What is central dogma?

Central dogma is the main process of the formation of the proteins from the nucleotide message of the DNA. Central dogma consists of the two main processes, which are transcription of DNA into the mRNA and translation of this mRNA into the protein.

What are mutations?

Mutations are the alternations in the codon sequences of the genes, which results in abnormal synthesis of protein products. There are many further divisions of the mutations, classified according to the extent of alternations and the mechanism of alternations. Frame-shift mutation is also a type of mutation resulting from the alternation in the nucleotide sequence of the coding genes.

Frame-Shift Mutation

If one or two nucleotides are either added to or deleted from the coding region of the coding sequence, it is termed as frame-shift mutation, as it changes the reading frame. The malformed product is the result of the radically altered amino acid sequence. The frame-shift mutation can also produce a truncated product due to the formation of termination codons.

The mutations resulting from nucleotide substitutions do not affect the neighboring codons of the DNA, but the mutations resulting from the insertions or deletions cause the entire reading frame of the gene to be changed.

Missense mutation resulting from frame-shift mutations

Two frame-shift mutations can cancel each other, as the addition of one nucleotide at a location on the gene sequence can be counterbalanced by the deletion of another nucleotide along the coding sequence. In such conditions, the result will be a missense mutation.missense-1

Frame-shift mutation is different from the single nucleotide polymorphism, in which the nucleotide is actually replaced rather than deleted or inserted. The frame-shift mutation will result in altered codon and different amino acids. In this way, the created polypeptide chain will either be too long or too short, and the polypeptide chain produced by the frame-shift mutation will not be functional. 

If three nucleotides are added, the produced peptide will contain one more amino acid. Similarly, if three nucleotides are deleted, the resulting peptide will lose one amino acid. If three nucleotides are lost, the reading frame will still be maintained but it can result in serious pathological conditions.

Examples of Frame-shift mutations

  1. Cystic fibrosis (CF) is a hereditary disorder, in which the digestive and the pulmonary systems are affected. Its most common cause is the deletion of three nucleotides from the coding region of the gene. In cystic fibrosis, the loss of three nucleotides results in the loss of phenylalanine at the 508th position in the encoded protein. This mutation at the 508th position of protein prevents the normal folding of the trans-membrane conductance regulator protein (CFTR), which leads to its destruction by the proteasome. The cystic fibrotic trans-membrane regulator (CFTR) normally functions as a chloride channel in the epithelial cells. The loss of CFTR results in the production of sticky, thick secretions in the pancreas and the lungs, leading to digestive  and lung deficiencies. This 508th position mutation is the cause of the disease in 70% of Caucasians. 
  2. Tay-Sachs disease is a severe genetic disorder produced as a result of frame-shift mutation. In this disease, the susceptibility to certain classes of familial hypercholesterolemia and cancers is increased.
  3. The resistance to the infection by the HIV retrovirus was reported to be linked with frame-shift mutation in 1997.
  4. Cancers of the colorectal region are associated with frame-shift mutations. The incidence of frame-shift mutation occurs more in the regions of repeat sequence. Frame-shift mutations also play an important role in the development of breast and ovarian cancer due to over 500 mutations in chromosome 17 in the BRCA1 gene.
  5. Crohn’s disease is associated with the NOD2 gene due to insertion of cytosine at position 320. It is also the consequence of frame-shift mutation.

Detection of frame-shift mutations

Frame-shift mutations can be detected by Fluorescence and Sequencing. In the fluorescence method, fluorescently tagged DNA enables us, by means of base analogues, to study the local changes of the DNA sequence. While in sequencing method, pyrosequencing and Sanger sequencing are the two methods used for detecting frame-shift mutations.

Cures for diseases caused by frame-shift mutations

The cure for the diseases caused by the frame-shift mutations is rare. However, research work is being done worldwide for finding the different mechanisms of treatment. The proposed mechanisms of treatment involve gene therapy, antisense oligonucleotide, mediated exon skipping, and revertant mosaicism. The use of immunotherapy for the treatment of frame-shift mutations is also under consideration.

Central Dogma Theory Script

1.Zoom: Top image

Hot Spot: Nuclear Library - Nucleus

Learning: The Central Dogma Theory of molecular biology describes the two-step process, transcription and translation by which information in genes flows into proteins. In other words, the information moves from DNA to RNA to the protein. This CoursePic takes the word dogma and associates it with dog and ma. We use Chrome Zombies to represent the word chromosomes and we use the nuclear symbol to remind us that the action is taking place inside the nucleus of the cell. There are 46 chromosomes in humans, so the clock provides a helpful reminder of this number.

Story: It’s well known that zombies, being dead and all, have a hard time making friends. So the Chrome Zombies have decided to build pet dogs for all the zombies who are lonely and want a companion. They decide that female dogs will be more friendly, so they set off to the Dog Center to learn how to make a dog ma. They locate the library, named the Nuclear Library, and search all the books for more information. Because the library is powered with nuclear energy, it can be dangerous for anyone to stay in the room for long periods. A countdown clock on the shelf reads 46 minutes, so the Chrome Zombies need to hurry.

2. Zoom: Top image, middle of picture

Hot Spot: Transcribers = transcription

Learning: The first step is transcription, which is the synthesis of an RNA copy from a segment of DNA. So, the double-stranded DNA molecule is partly unzipped and an enzyme called RNA polymerase copies the gene’s nucleotides one by one into an RNA molecule. It is often described as a being like a process of copying notes out of a library book, hence the CoursePic drawing. The RNA is like a notebook compared with the DNA represented by the entire contents of the library. This step occurs in the nucleus of a cell to produce a mRNA, or messenger RNA, molecule. The mRNA exits the nucleus and is translated in the cytoplasm. In this image, we see the transcription depicted as a deciphering action by the library’s transcribers. Their heads have the appearance of a T. The Messenger Boy represents the messenger RNA.

Story: As the Chrome Zombies look through the books on how to build a dog ma, one of them finds a book on the topic, but she can’t read the writing. It is written in a symbolic language unknown to her, so she goes to the checkout desk to ask the Professional T Protein Transcribers for help. One of the Transcribers pulls the symbols from the book into his transcription machine. When the transcription comes out, it reveals full instructions on how to order dog parts. Fantastic! The other Professional T Protein Transcriber fills out an order form and hands this to a Messenger Boy.

3. Zoom: Top image, man at the doorway

Hot Spot: Messenger Boy – Messenger RNA

Learning: The Messenger Boy exits the Nuclear Library with the information into the Cytoplasm Plaza, suggestive of a mRNA moving from the nucleus into the cytoplasm for further processing.

Story: The Messenger Boy takes the order form and heads for the door to the exit. This envelope door leads to the Cytoplasm Plaza where most of the library workers take their lunch. The floor of the plaza is painted yellow, a soothing color that helps the workers relax. The Messenger Boy must spend long periods at the Nuclear Library and, therefore, wears a yellow nuclear suit. He worries that this is not fully protecting him. He’s lost a lot of weight lately and, in fact, we can see his ribs through his suit. 

4. Zoom: Bottom image, lower left

Hot Spot: Translator - Translation

Learning: Translation is the second stage of the Central Dogma Theory. This involves RNA relaying information to the protein. The illustration shows a pro team, suggesting protein, receiving the delivery at the dog ma factory. The floor of the assembly line is the same yellow color as the Cytoplasm Plaza. Translation is depicted by the translator who interprets the instructions from the mail man to the Chrome Zombies.

Story: Here we see the Chrome Zombies’ dog ma factory, run by a pro team. The mailman is in the process of dropping off many boxes from the dog ma parts store. Once again, there is a language problem. The mailman and the Zombies do not always understand each other. So, they have a translator on hand to interpret any misunderstood communications.

5. Zoom: Bottom image, lower right

Hot Spot: Two Chrome Zombies with ribs showing - Ribosomes

Learning: In the cytoplasm, the ribosome translates RNA sequence information into an amino acid sequence. This includes both large and small ribosomes. Here, we see the floor color of the assembly line resembling the cytoplasm area from before. The pro team includes large and small Chrome Zombies with their ribs showing.

Story: As they receive the many boxes of dog parts, the Chrome Zombies unpack these and place the contents into bins on rollers. These will be added to a train for assembly. Notice that the factory employs a wide variety of Chrome Zombies. Some are small and some are large.

6. Zoom: Bottom image, top portion

Hot Spot: Train - tRNA

Learning: Transfer RNA, abbreviated as tRNA, brings amino acids to ribosomes during the translation process. Here, the tRNA is linked with the word train, which is bringing materials to the ribbed Zombies working during the translation process. The result is the completed dog ma, or dogma.

Story: The assembly line consists of a train carrying dog parts from the receiving dock to the production line. Here, we see the train and two of the Chrome Zombies working on the final stage of assembly. Once the head is placed on the assembled body and a decorative collar is attached, each dog ma is ready to find a grateful best friend!

 

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